Diethylstilbestrol (DES) was developed in the 1940s on the assumption that it prevented pregnancy complications, namely miscarriage. However, by the 1970s it was found that this was a false assumption, and soon it was realized that its usage was associated in young women with the occurrence of genital tract adenosis and of rare adenocarcinomas of the vagina and cervix in those who had been exposed in utero to DES. Now nearly four decades later the genital tract complications have virtually disappeared but more sinister genital and extragenital problems in this unfortunate cohort group are developing and will be discussed below.

During the intrauterine life of the female fetus, the paired Müllerian paramesonephric ducts arise from the urogenital ridges, extend caudally, and then fuse at the urogenital sinus. This column of cells is replaced by a solid core of squamous epithelium that arises from the vaginal plate. The vaginal plate grows from the urogenital sinus, extends along the paired Müllerian ducts, and develops to form the major part of the vagina and cervix. In the newly born female child, the junction between the glandular Müllerian epithelium and the squamous epithelium extending from the urogenital sinus lies close to the external os of the cervix. The position of the squamocolumnar junction is quite variable.

In the normal young girl, the vagina does not contain any glandular elements, except for occasional remnants that lie in the deep tissues and may form cystic structures (Gartner’s duct cysts) at a later date.

From time to time, congenital variations of this development occur and remnants of the columnar epithelium may extend from the cervix onto the upper vagina, usually in an anteroposterior line. Later squamous metaplasia occurs in this area, producing the so-called congenital acetowhite changes (or congenital transformation zone) that are seen in a small number of individuals. Approximately 2.5% of women will have a squamocolumnar junction that extends from the cervix onto the vagina. Vaginal adenosis is a further variation of this development in that glandular epithelium is present in the vagina; this epithelium is of an endocervical type. It can either be on the surface, replacing the normal squamous epithelium, or occur as mucus-secreting cystic glands and crypts in the dermis. In1971, it was recognized for the first time that maternal ingestion of DES could lead to the development in female offspring of extensive cervicovaginal adenosis and rarely to adenocarcinoma of the vagina. DES was first produced in 1938 and was in clinical use by the mid-1940s. Since 1971, vaginal adenosis has been reported mainly in association with prenatal exposure to DES, but still may occur in women without such exposure. Adenosis found in females born prior to the DES era is similar in type to that found in women exposed to DES.

The widespread use of colposcopy has meant that small areas of surface adenosis have been noted in asymptomatic women who have no history of DES exposure. The symptoms, when present, include profuse mucoid vaginal discharge, soreness, and/or postcoital bleeding resulting from the fragile and exposed glandular epithelium. The symptoms can be distressing and lead to concern about malignancy. Although an uncommon condition, it has been seen by the authors with increasing frequency and in two cases, seen by one of us (A.S.), it has been associated with pregnancy in which a postpartum hemorrhage necessitated the use of a vaginal pack. In both women, vaginal adenosis developed within 6 months; in one such case it was associated with erosive lichen planus of the vulva and vagina. Lichen planus in association with vaginal adenosis is also not very uncommon. Ingestion of DES and its effects on the offspring of women taking it had a profound effect on gynecology, especially in the USA, during the 1970s and 1980s. In the following section, the developmental anomalies caused by this drug will be discussed, and the clinical management will also be considered.

The role of DES as a teratogen has been confirmed in other species. DES might act on the stroma and this could result in the production of some of the morphologic deformities and epithelial abnormalities of connective tissue that were seen in women exposed to DES. The increased risk of clear cell adenocarcinoma in the offspring of such women, especially those exposed in early pregnancy, may be due to large areas of the ectopic columnar epithelium in the vagina undergoing inductive changes, as described above.